The innate immune response to virus infection has a strong influence on virus infection in the brain and the clinical outcome of disease. Our studies have focused on two animal models of virus-mediated neuropathogenesis to determine the host response proteins that regulate disease induction for virus replication and viral pathogenesis. In FY2016, we examined multiple mechanisms of virus-induced parthenogenesis in the CNS. This included the activation of microglia/astrocytes and the recruitment of monocytes. We studied activation of both microglia and astrocytes following TLR activation or virus infection (both bunyavirus and retrovirus infection), examining transcriptome changes to identify markers of glial activation associated with disease (Madeddu et al. PLoS One 2015). We also collaborated with other investigators to examine mediators of glial activation in other diseases (Liu et al. Scientific Reports 2016; Carroll et al. PLoS Pathogens 2016). We examined the influence of innate immune responses on neurons and found that neurons through the expression of Neuropeptide Y (NPY) could influence the recruitment of immune cells to the CNS (Woods et al. J. Virol. 2016). Finally, we also looked at how innate immune stimulation directly affected neurons and demonstrated that activation of neurons by innate immune signaling pathways induced apoptosis through a SARM1-dependent mechanism, which was associated with dysregulation of mitochondria trafficking (Mukherjee et al. J. Immunol. 2015).